This application is based on the hypothesis that unloading arterial baroreceptors can cause hypertension. We have developed a model with carotid baroreceptors on one side functional (all other carotid and aortic baroreceptors denervated) in conscious dogs. In this model, ligation of the common carotid artery proximal to the innervated carotid sinus produces a significant and sustained increase in systemic arterial pressure (SAP, 22 +/- 3 mmHg for at least seven days duration, n=6) and plasma renin activity (PRA). Carotid ligation unloads baroreceptors downstream and the reflex increase in SAP returns mean carotid sinus pressure (CSP) to control levels. The cause of the increase in SAP must be related to unloading carotid baroreceptors because removing the ligature on the innervated side after seven days results in a reduction in SAP to control levels. Furthermore, ligation of the common carotid on the denervated side results in a fall in CSP distal to the ligature and does not cause an increase in SAP (n=4). The goal of this application is to elucidate the mechanisms, which drive the hypertension in this model. The aims are first, to extend the observations to include continuous measurements of SAP with the animals in their home cages using telemetry. The second aim is to test the hypothesis that the renal nerves are essential for the maintenance of the hypertension. Carotid baroreceptors will be unloaded as above in dogs with denervated kidneys. The third aim will test the hypothesis that the hypertension is primarily due to an increase in peripheral resistance by measuring cardiac output and pressure simultaneously. The fourth aim will test the hypothesis that increased sympathetic efferent activity is responsible for the hypertension. Control experiments will utilize ligation of the carotid proximal to a denervated carotid sinus. The health implications of this project are startling because current theories disregard participation of baroreceptors in the long-term control of blood pressure. These studies will provide a new framework for understanding the development and maintenance of hypertension.